Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase Ill trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4x epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4x docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6x epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy

Histone H3 Lysine 9 Acetylation is Downregulated in GDM Placentas and Calcitriol Supplementation Enhanced This Effect

Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study's objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell's transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol

Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients

Background: Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. Methods: Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. Results: We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8\%) patients were female, 117 (45.2\%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6\% with anemia, 44.8\% with endocrine diseases, 12.4\% with internal malignancies, 9.3\% with chronic inflammatory bowel diseases and 4.3\% with elevated creatinine levels. Moreover 25.5\% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. Conclusions: Our study describes one of the world's largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients' characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients

Sociodemographic variables, clinical features, and the role of preassessment cross-sex hormones in older trans people

Introduction: As referrals to gender identity clinics have increased dramatically over the last few years, no studies focusing on older trans people seeking treatment are available. Aims: The aim of this study was to investigate the sociodemographic and clinical characteristics of older trans people attending a national service and to investigate the influence of cross-sex hormones (CHT) on psychopathology. Methods: Individuals over the age of 50 years old referred to a national gender identity clinic during a 30-month period were invited to complete a battery of questionnaires to measure psychopathology and clinical characteristics. Individuals on cross-sex hormones prior to the assessment were compared with those not on treatment for different variables measuring psychopathology. Main Outcome Measures: Sociodemographic and clinical variables and measures of depression and anxiety (Hospital Anxiety and Depression Scale), self-esteem (Rosenberg Self-Esteem Scale), victimization (Experiences of Transphobia Scale), social support (Multidimensional Scale of Perceived Social Support), interpersonal functioning (Inventory of Interpersonal Problems), and nonsuicidal self-injury (Self-Injury Questionnaire). Results: The sex ratio of trans females aged 50 years and older compared to trans males was 23.7:1. Trans males were removed for the analysis due to their small number (n ¼ 3). Participants included 71 trans females over the age of 50, of whom the vast majority were white, employed or retired, and divorced and had children. Trans females on CHT who came out as trans and transitioned at an earlier age were significantly less anxious, reported higher levels of self-esteem, and presented with fewer socialization problems. When controlling for socialization problems, differences in levels of anxiety but not self-esteem remained. Conclusion: The use of cross-sex hormones prior to seeking treatment is widespread among older trans females and appears to be associated with psychological benefits. Existing barriers to access CHT for older trans people may need to be re-examined

Dopamina e comportamento alimentar: polimorfismos em receptores dopaminérgicos e fenótipos relacionados à obesidade

Dentre os sistemas neurais responsáveis pela ingestão dos alimentos, destaca-se a via dopaminérgica mesolímbica que, através da liberação de dopamina nos núcleos de accumbens, desperta prazer e motivação para recompensas químicas e naturais. Esta via de recompensa age através dos receptores dopaminérgicos transmembranares, que variam de DRD1 a DRD5. Desta forma, considerando os efeitos prazerosos despertados pela ingestão alimentar, é plausível que variações genéticas em genes do sistema dopaminérgico possam ter um papel na arquitetura genética da obesidade. Este estudo tem como objetivo realizar uma revisão narrativa da literatura sobre a influência de variantes genéticas nos receptores dopaminérgicos em fenótipos relacionados com a obesidade. Em conjunto, os principais achados desta revisão indicaram que os genes codificadores dos receptores DRD2 e DRD4 possam ser os mais relevantes no contexto da obesidade e fenótipos relacionados. No entanto, a obesidade é uma doença complexa e multifatorial e novos estudos são ainda necessários para uma melhor compreensão do impacto da dopamina nos desfechos relacionado à obesidade. É importante também destacar que esses efeitos podem ser específicos para subgrupos de pacientes e que outros fatores, além das variantes genéticas, devem ser considerados

Dopamina e comportamento alimentar: polimorfismos em receptores dopaminérgicos e fenótipos relacionados à obesidade

Dentre os sistemas neurais responsáveis pela ingestão dos alimentos, destaca-se a via dopaminérgica mesolímbica que, através da liberação de dopamina nos núcleos de accumbens, desperta prazer e motivação para recompensas químicas e naturais. Esta via de recompensa age através dos receptores dopaminérgicos transmembranares, que variam de DRD1 a DRD5. Desta forma, considerando os efeitos prazerosos despertados pela ingestão alimentar, é plausível que variações genéticas em genes do sistema dopaminérgico possam ter um papel na arquitetura genética da obesidade. Este estudo tem como objetivo realizar uma revisão narrativa da literatura sobre a influência de variantes genéticas nos receptores dopaminérgicos em fenótipos relacionados com a obesidade. Em conjunto, os principais achados desta revisão indicaram que os genes codificadores dos receptores DRD2 e DRD4 possam ser os mais relevantes no contexto da obesidade e fenótipos relacionados. No entanto, a obesidade é uma doença complexa e multifatorial e novos estudos são ainda necessários para uma melhor compreensão do impacto da dopamina nos desfechos relacionado à obesidade. É importante também destacar que esses efeitos podem ser específicos para subgrupos de pacientes e que outros fatores, além das variantes genéticas, devem ser considerados

Borderline personality and the detection of angry faces

BACKGROUND:Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients' ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients' ability to detect angry faces. METHODS:To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n1 = 342, n2 = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured. RESULTS:Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects. CONCLUSIONS:In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed

Synthesis and Characterization of Rigid Ditopic N-Heterocyclic Benzobisgermylenes and -stannylenes

A rigid ditopic benzobisgermylene, <b>4a</b>, was prepared by the reaction of the 1,2,4,5-tetra(alkylamine)­benzene <b>3a</b> and Ge­[N­(SiMe₃)₂]₂. The analogous reaction of two 1,2,4,5-tetra(alkylamine)­­benzenes, <b>3b</b>,<b>c</b>, with Sn­[N­(SiMe₃)₂]₂ led to the oxidation of the tetramine ligand and formation of <i>N</i>-alkyl-2-(alkylamine)-<i>N′</i>-alkyl-5-(alkylamine)-1,4-benzoquinonediimines (<b>5b</b>,<b>c</b>) and tin(0). The <i>p</i>-benzoquinonediimines <b>5b</b>,<b>c</b> subsequently react with remaining Sn­[N­(SiMe₃)₂]₂ to yield distannylene complexes of type [<i>N</i>-alkyl-2-(alkylamino)-<i>N′</i>-alkyl-5-(alkylamino)-1,4-benzoquinonediimine]­di­[bis­(trimethylsilyl)­aminotin­(II)] (<b>6b</b>,<b>c</b>). The 2,5-di­(alkylamine)-1,4-benzoquinonediimines <b>5b</b>,<b>c</b> can also be obtained directly by aerial oxidation of the 1,2,4,5-tetrakis­(alkylamine)­benzenes <b>3b</b>,<b>c</b>. They react with two equivalents of Sn­[N­(SiMe₃)₂]₂ also under transmetalation and formation of [<i>N</i>-alkyl-2-(alkylamino)-<i>N′</i>-alkyl-5-(alkylamino)-1,4-benzoquinonediimine]­di­[bis­(trimethylsilyl)­aminotin­(II)] (<b>6b</b>,<b>c</b>). The molecular structures of <b>3b</b>, <b>4a</b>, <b>6b</b>, and <b>6c</b> have been established by X-ray diffraction

The German SUCCESS C Study – The First European Lifestyle Study on Breast Cancer

Cohort trials have shown evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients. The SUCCESS C study is the first European trial to evaluate the effect of an intensive lifestyle intervention program on disease-free survival in women with early breast cancer and to examine the predictive value of selected biomarker candidates. A total of 3,547 women with early-stage, Her2/neu-negative breast cancer will be included. The first randomization will compare disease-free survival in patients treated with either 3 cycles of FEC (epirubicine, fluorouracil, cyclophosphamide), followed by 3 cycles of docetaxel or 6 cycles of docetaxel-cyclophosphamide, and thus assess the role of anthracycline-free chemotherapy. The second randomization compares disease-free survival in patients with a body mass index of 24–40 kg/m2 receiving either a telephone- based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. In addition, the study will evaluate the predictive role of cancer-associated and obesity-related biomarkers for the prediction of disease recurrence and survival. This SUCCESS C trial will provide valuable information on the effects of a lifestyle intervention program on the prognosis of early breast cancer patients.Aktuelle Studien deuten darauf hin, dass Adipositas und ein Mangel an körperlicher Aktivität nicht nur mit einem erhöhten Risiko assoziiert sind, an einem Mammakarzinom zu erkranken, sondern auch nach der Erkrankung mit einer gesteigerten Rezidivrate und Mortalität einhergehen. Die SUCCESS C-Studie ist die erste europäische Studie, die den Einfluss eines intensivierten Lebensstilinterventionsprogramms auf das krankheitsfreie Überleben von Frauen mit frühem Mammakarzinom untersucht. Außerdem werden ausgewählte Biomarker getestet. Insgesamt werden 3.547 Frauen mit frühem, Her2/neu-negativen Mammakarzinom eingeschlossen. In der ersten Randomisation wird das krankheitsfreie Überleben unter einer Therapie mit entweder 3 Zyklen FEC (Epirubicin, Fluorouracil, Cyclophosphamid), gefolgt von 3 Zyklen Docetaxel oder 6 Zyklen Docetaxel-Cyclophosphamid verglichen, und damit die Rolle einer anthrazyklinfreien Chemotherapie in diesem Kollektiv geprüft. Die zweite Randomisation vergleicht das krankheitsfreie Überleben von Patientinnen mit einem Body Mass Index von 24–40 kg/m2, die entweder ein telefonbasiertes Lebensstilinterventionsprogramm mit dem Ziel einer moderaten Gewichtsabnahme oder lediglich allgemeine Informationen für eine gesunde Lebensführung erhalten. Zusätzlich zur klinischen Fragestellung werden brustkrebs- oder adipositasassoziierte Biomarker auf ihre prognostische und prädiktive Wertigkeit hin geprüft. Die SUCCESS C-Studie wird wertvolle Informationen zur Effektivität eines Lebensstilinterventionsprogramms zur Prognoseverbesserung bei Mammakarzinompatientinnen liefern